AnB block copolymers containing poly (vinyl pyrrolidone) units, medical devices, and methods

ABSTRACT

A n B block copolymers, wherein n is at least two, that include A blocks with poly(vinyl pyrrolidone) units and B blocks with urethane groups, urea groups, imide groups, amide groups, ether groups, ester groups, or combinations thereof, as well as medical devices and methods.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.10/246,806, filed on Sep. 17, 2002 now U.S. Pat. No. 6,756,449, whichclaims priority to U.S. Provisional Application No. 60/360,725, filed onFeb. 27, 2002, both of which are incorporated herein by reference intheir entireties.

FIELD OF THE INVENTION

This invention relates to polymers containing poly(vinyl pyrrolidone)copolymerized with other polymers such as polyurethanes, etc. Suchmaterials are particularly useful as biomaterials in medical devices.

BACKGROUND OF THE INVENTION

The chemistry of block copolymers is extensive and well developed. Theycan be used to combine the properties of different polymers in onematerial. For example, a polymer having hydrophilic properties can formone block and a polymer having hydrophobic properties can form anotherblock. Thus, one material can have combinations of properties thatneither constituent polymer possesses alone. This can be of significantutility in the medical device arena.

Polymers used to create medical devices are typically chosen for theirbulk properties; however, it is often desirable for the surfaces of suchmedical devices to possess different properties than that of the bulkpolymer. For example, it may be desirable for a polymer surface to havea different level of compatibility with other polymers or tissues,surface energy, etc., than that of the bulk polymer. Thus, blockcopolymers are desirable materials to investigate for their utility inmodifying polymer surfaces for medical device applications.

Block copolymers have been used to modify polyurethane surfaces, whichare important biomedical polymers used in implantable devices such asartificial hearts, cardiovascular catheters, pacemaker lead insulation,etc. Such block copolymers have been used to enhance antimicrobialproperties, lubricity, barrier properties, anticoagulant properties, andthe like. For example, U.S. Pat. No. 4,675,361 (Ward, Jr.) discloses ablock copolymer for improved biocompatibility. Also, U.S. Pat. No.5,302,385 (Khan et al.) discloses a polyurethane-poly(vinyl pyrrolidone)copolymer foam having antimicrobial properties coated on a catheter. Theresultant polymer is highly branched or a network polymer without awell-defined or controllable block architecture.

Other block copolymers are needed for modifying the surface propertiesof medical devices.

SUMMARY OF THE INVENTION

The present invention relates to block copolymers, particularly A_(n)Bblock copolymers, wherein n is at least two, and more particularly A-B-Ablock (triblock) copolymers, that include poly(vinyl pyrrolidone) in theA blocks, and urethane groups, urea groups, amide groups, imide groups,ester groups, ether groups, or combinations thereof (e.g.,polyurethanes, polyureas, or polyurethane-ureas) in the B block. Thisincludes methods for making such polymers.

The block copolymers of the present invention are particularly useful asbiomaterials in medical devices. Certain preferred embodiments of theblock copolymers can also provide a lubricious surface (e.g., a slipcoating on a polymeric surface). Lubricous surfaces are desirable formany medical devices, particularly the inner surfaces of lead deliverycatheters. Coating conventional materials on the inner surfaces of suchcatheters can be difficult and expensive, however. The block copolymersof the present invention provide an opportunity to more easilymanufacture such devices. Methods involving dip coating followed bysolvent removal techniques can be used to apply the block copolymers ofthe present invention to a substrate. Alternatively, the blockcopolymers can be coextruded with another thermoplastic polymer to forma layered construction. Extrusion methods can also involve reactivecoextrusion.

In one embodiment, the present invention provides a thermoplastic A_(n)Bblock copolymer, wherein the A blocks include poly(vinyl pyrrolidone)units and the B block is a long-chain organic connecting unit thatincludes urethane groups, urea groups, imide groups, amide groups, ethergroups, or combinations thereof, wherein n is at least two.

The present invention provides medical devices. One such device includesa surface that includes a thermoplastic A_(n)B block copolymer, whereinthe A block includes poly(vinyl pyrrolidone) units and the B block is along-chain organic connecting unit that includes urethane groups, ureagroups, imide groups, amide groups, ester groups, ether groups, orcombinations thereof, wherein n is at least two. The “surface” can bethe surface of a coating, for example, of a thermoplastic A_(n)B blockcopolymer on another substrate, such as a polymeric material.Alternatively, the “surface” can be the surface of an extruded layer,for example, of a thermoplastic A_(n)B block copolymer, which can becoextruded with another polymeric material, or formed using reactivecoextrusion.

The present invention also provides methods of modifying a surface of amedical device. One method includes: preparing a thermoplastic A_(n)Bblock copolymer, wherein the A block includes poly(vinyl pyrrolidone)units and the B block is a long-chain organic connecting unit thatincludes urethane groups, urea groups, imide groups, amide groups, ethergroups, ester groups, or combinations thereof, wherein n is at leasttwo; and applying the A_(n)B copolymer to the surface of the medicaldevice.

The present invention also provides methods of preparing a thermoplasticA_(n)B block copolymer. One method includes reacting a substantiallymonofunctional poly(vinyl pyrrolidone) with a functionalized B-blockprecursor that includes functional groups reactive with the functionalgroups of the poly(vinyl pyrrolidone) to form the thermoplastic A_(n)Bblock copolymer. In an alternative method, the block copolymer is madein one step using a substantially monofunctional poly(vinyl pyrrolidone)with reactants for the functionalized B-block precursor.

As used herein, the term “organic group” refers to a hydrocarbyl group(aliphatic and/or aromatic) optionally including other atoms (e.g.,heteroatoms) or groups (e.g., functional groups) replacing the carbonand/or hydrogen atoms. The term “aliphatic group” means a saturated orunsaturated linear (i.e., straight chain), cyclic, or branchedhydrocarbon group. This term is used to encompass alkyl (e.g., —CH₃) (oralkylene if within a chain such as —CH₂—), alkenyl (or alkenylene ifwithin a chain), and alkynyl (or alkynylene if within a chain) groups,for example. The term “alkyl group” means a saturated linear or branchedhydrocarbon group including, for example, methyl, ethyl, isopropyl,t-butyl, heptyl, dodecyl, octadecyl, amyl, 2-ethylhexyl, and the like.The term “alkenyl group” means an unsaturated, linear or branchedhydrocarbon group with one or more carbon-carbon double bonds, such as avinyl group. The term “alkynyl group” means an unsaturated, linear orbranched hydrocarbon group with one or more carbon-carbon triple bonds.The term “aromatic group” or “aryl group” means a mono- or polynucleararomatic hydrocarbon group. These hydrocarbon groups may be substitutedwith heteroatoms, which can be in the form of functional groups. Theterm “heteroatom” means an element other than carbon (e.g., nitrogen,oxygen, sulfur, chlorine, etc.).

As used herein, the terms “a,” “an,” “one or more,” and “at least one”are used interchangeably.

As used herein, a “thermoplastic” polymer is one that will melt and flowwhen heated and reform substantially the same material upon cooling.

As used herein, a “biomaterial” or “biocompatible material” may bedefined as a material that is substantially insoluble in body fluids andtissues and that is designed and constructed to be placed in or onto thebody or to contact fluid or tissue of the body. Ideally, a biocompatiblematerial will not induce undesirable reactions in the body such as bloodclotting, tissue death, tumor formation, allergic reaction, foreign bodyreaction (rejection) or inflammatory reaction; will have the physicalproperties such as strength, elasticity, permeability, and flexibilityrequired to function for the intended purpose; can be purified,fabricated, and sterilized easily; and will substantially maintain itsphysical properties and function during the time that it remainsimplanted in or in contact with the body.

As used herein, a “medical device” may be defined as an article that hassurfaces that contact blood or other bodily tissues in the course oftheir operation. This can include, for example, extracorporeal devicesfor use in surgery such as blood oxygenators, blood pumps, bloodsensors, tubing used to carry blood, and the like, which contact blood,which is then returned to the patient. This can also include implantabledevices such as vascular grafts, stents, electrical stimulation leads,heart valves, orthopedic devices, catheters, guide wires, shunts,sensors, replacement devices for nucleus pulposus, cochlear or middleear implants, intraocular lenses, and the like.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS OF THE INVENTION

The present invention provides polymers, medical devices that includesuch polymers (preferably, biomaterials), and methods of making andusing such polymers. Such polymers are suitable for modifying thesurface of a substrate, such as in or on a medical device. Suchsubstrates include, for example, polymers such as polyurethanes,polyureas, poly(urethane-urea)s, polyamides, poly(amide-ether)s,polyimides, copolymers or mixtures thereof.

One medical device of particular interest is a catheter such as a leaddelivery catheter. Preferably, the inner lumen of the catheter is coatedwith a polymer of the present invention.

The polymers are preferably A_(n)B block copolymers, wherein n is atleast two, and more preferably A-B-A block copolymers. Each “block” orsegment may be a homopolymer, or a random or block copolymer itself. Forexample, the A block can include one or more poly(vinyl pyrrolidone)(PVP) units, optionally polymerized with other monomers. The B block caninclude urethane groups, urea groups, amide groups, imide groups, estergroups, ether groups, or combinations thereof. The B block preferablyincludes urethane groups, urea groups, amide groups, imide groups, ethergroups, or combinations thereof. More preferably, the B block includesurethane groups and/or urea groups. Most preferably, the B blockincludes urethane groups.

Typically, the A_(n)B block copolymers are prepared from precursorpolymers (i.e., prepolymers), although other methods can be used tobuild polymers with the same block architecture. In a particularlypreferred embodiment, the B block is formed from an isocyanatefunctional prepolymer (e.g., a diisocyanate polyurethane (OCN-PU-NCO))and the A block is formed from a substantially monofunctional hydroxylterminated poly(vinyl pyrrolidone) prepolymer (PVP-OH). In this A_(n)Bformulation, the B block is defined to include the functionality formedupon reaction of the A and B prepolymers (e.g., PVP-OH and OCN-PU-NCOprepolymers).

In an exemplary schematic, a preferred A_(n)B block copolymer is anA-B-A block copolymer, which can be formed according to the followingscheme (Scheme I):

wherein:

X and Y contain at least one reactive functionality selected from thegroup consisting of primary or secondary amine groups, primary orsecondary amides, carboxylic acid groups, hydroxyl groups (e.g.,phenols), isocyanate groups, wherein X and Y are selected to be reactivewith each other;

Z contains urethane groups, urea groups (e.g., acyl ureas), amidegroups, imide groups, ester groups, ether groups, or combinationsthereof;

R is a long chain organic (connecting) group; and

PVP-X is a polymer formed from N-vinyl pyrrolidone and other optionalmonomers.

Each of the individual A and B blocks, as well as the resultant polymer,may be linear or branched, although not so significantly branched thatthe resultant polymer is not thermoplastic. Preferably, the A and Bblocks are both linear, as is the resultant polymer. Because the B blockcan be branched, it is envisioned that the A_(n)B block copolymer couldbe a star block copolymer, for example, wherein n is at least three.

Preferably, the block copolymer of the present invention has a weightaverage molecular weight of at least about 1000 grams per mole (g/mol),more preferably, at least about 10,000 g/mol in the uncrosslinked state,and most preferably, at least about 20,000 g/mol. Preferably, the blockcopolymer of the present invention has a weight average molecular weightof no greater than about 3×10⁶ g/mol in the uncrosslinked state. Themolecular weights of the block copolymers can be controlled bywell-known synthetic techniques. Typically, for preferred embodiments,the molecular weights of the prepolymers control the final molecularweights of the block copolymers.

If desired, the block copolymer can be crosslinked after application toa surface, particularly a surface of a medical device. Crosslinking canbe accomplished using a variety of well-known techniques. This caninclude the use of electron beam (E-beam). Alternatively, it can beaccomplished through the incorporation of unsaturation in the B-blockand the use of chemical crosslinkers such as butanediol divinyl ether ordivinyl benzene.

If desired, the block copolymer can be mixed with a secondary polymerfor various effects. It is particularly desirable to use a constituentpolymer of the substrate on which this block copolymer is coated as thesecondary polymer to enhance adhesion to the substrate. Examples ofsuitable secondary polymers include a polyurethane, a polyurea, apoly(urethane-urea), a polyamide, a poly(amide-ether), a polyimide,copolymers or mixtures thereof. Alternatively, poly(vinyl pyrrolidone)can be used as the secondary polymer to further modify the surfaceproperties of the substrate polymer.

Preferably, the block copolymer is lubricious (e.g., slippery). This canbe evaluated qualitatively by finger touch. Alternatively, thecoefficient of friction (COF) can be determined on wet surfaces asdescribed in the Examples Section. Preferably, a lubricious coating hasa COF at least 50% less than, and more preferably, at least 80% lessthan, that of the uncoated substrate. Alternatively stated, morepreferably, the COF of a substrate having a lubricious coating thereonis 20% of the COF of the uncoated substrate or less.

Preferred A Blocks

The A blocks of the A_(n)B block copolymers wherein n is at least two,preferably A-B-A block copolymers, of the present invention includepoly(vinyl pyrrolidone) (PVP). PVP is particularly desirable because PVPhomopolymers of at least about 400,000 g/mol (weight average molecularweight) are generally lubricious and biocompatible. Surprisingly,however, lower molecular weight PVP-containing blocks can also providesuitable lubricity. Preferably, the PVP used to form the A blocks has aweight average molecular weight of at least about 1000 g/mol, and morepreferably at least about 1500 g/mol. Preferably, the PVP used to formthe A blocks has a weight average molecular weight of no greater thanabout 1×10⁶ g/mol, more preferably, no greater than about 500,000 g/mol,even more preferably, no greater than about 400,000 g/mol, and mostpreferably, no greater than about 200,000 g/mol.

If desired, the A blocks of the A_(n)B block copolymers of the presentinvention could include copolymers of N-vinyl pyrrolidone (i.e.,1-vinyl-2-pyrrolidone) and monomers nonreactive with isocyanate groupsor other reactive functional groups on the B-block prepolymer (Y inScheme I above). Such monomers are selected from the group consisting of(meth)acrylic esters (i.e., acrylic esters and methacrylic esters, alsoreferred to as (meth)acrylates), (meth)acrylamides. (i.e., acrylamidesand methacrylamides), butadiene, ethylene, alpha-olefins, halogenatedolefins (e.g., tetrafluoroethylene), acrylonitrile, isoprene, styrene,vinyl chloride, vinyl fluoride, vinyl esters, vinylidene chloride,N-vinyl carbazole, and combinations thereof. Thus, as used herein a“PVP” prepolymer or “PVP” block is defined as one that includes apolymer of N-vinyl pyrrolidone or copolymers thereof with one or moreother monomers. Preferably, a PVP prepolymer or PVP block includes onlypoly(vinyl pyrrolidone).

The A blocks of the A_(n)B block copolymers of the present invention arepreferably formed from a substantially monofunctional PVP prepolymer. Bythis it is meant that the PVP prepolymer starting material could havesmall amounts of difunctional PVP or nonfunctional PVP, although it isprimarily monofunctional PVP.

Preferably, the functionalized PVP prepolymer is hydroxyl terminated.Although substantially monofunctional hydroxyl terminated PVP ispreferred, other functionalized PVPs could be used to form the A blocksof the A_(n)B block copolymers of the present invention (e.g., could beany of the X groups in Scheme I above). Preferably, PVP prepolymers(which can be homopolymers or copolymers) could be functionalized withprimary or secondary amine groups, carboxylic acid groups, as well ashydroxyls (e.g., phenols), and combinations thereof. More preferably,PVP prepolymers are functionalized with hydroxyl. It should beunderstood that the PVP-X prepolymers can include other functionality inthe X moiety, particularly ether functionality (e.g., —X can be—C(CH₃)₂—O—CH₂C(O)OH or —C(CH₃)₂—O—CH₂CH₂OH).

The A blocks can be linear or branched. Preferably, they are linear. Abranched A block, for example, could be prepared from a PVP-OHprepolymer reacted with citric acid to form the corresponding triesteraccording to the following schematic (Scheme II):

Preferred B Block

The B block of the A_(n)B block copolymers wherein n is at least two,preferably the A-B-A block copolymers, is a long-chain organicconnecting unit between the A blocks. The B block is typically designedto be compatible with, and to adhere to, a particular surface. Forexample, the B block can be designed to penetrate an underlyingpolymeric surface and through physical entanglement improve adhesion ofthe block copolymer.

Typically, the B block is functionalized with urethane groups, ureagroups, amide groups, imide groups, ester groups, ether groups, orcombinations thereof. Preferably, the B blocks include urethane groups,urea groups (e.g., acyl urea groups), amide groups, imide groups, ethergroups, or combinations thereof. More preferably, the B blocks includeurethane groups and/or urea groups. Most preferably, the B blocksinclude urethane groups. The B blocks can optionally include tertiaryamine groups, siloxane groups, silane groups, ortho-ester groups,phosphoester groups, thioether groups, sulfoxide groups, sulfone groups,ketone groups, acetal groups, ketal groups, hemiacetal groups, hemiketalgroups, epoxy groups, and combinations thereof.

As used herein, “long-chain” refers to an organic connecting unit (i.e.,connecting the A blocks) containing 20 atoms or more (preferably, 20carbon atoms or more). Preferably, a B block includes about 100 atoms ormore, more preferably about 500 atoms or more, and most preferably about1000 atoms or more, connecting the A blocks. Preferably, there are nomore than about 1×10⁶ atoms in the chain.

Preferably, the precursor (which is preferably a prepolymer) used toform the B block is functionalized with at least two reactive groups,and more preferably only two reactive groups, which are preferablyisocyanate groups. Preferred materials are substantially polyfunctional(i.e., functionalized with groups reactive with the PVP prepolymer).More preferred materials are substantially difunctional. That is,“substantially” polyfunctional or difunctional means that there may besmall amounts of monofunctional or nonfunctional prepolymers present inthe precursor.

Although isocyanate functionality is preferred, other functionalizedprecursors could be used to form the B blocks of the A_(n)B blockcopolymers of the present invention (i.e., could be any of the Y groupsin Scheme I above). Preferably, they could be functionalized withcarboxylic acids, hydroxyl groups, primary or secondary amides, as wellas isocyanates. More preferably, the B block precursors arefunctionalized with isocyanates.

Upon reacting such functionalized precursors with functionalized PVPprepolymers, the resultant A_(n)B block copolymer would result inlinking groups (the Z functionality in Scheme I, which are incorporatedinto the B blocks according to the present invention) that include, forexample, urethane groups, urea groups (e.g., acyl ureas), amide groups,imide groups, ester groups, ether groups, or combinations thereof.Preferably, Z includes urethane groups, urea groups, amide groups, imidegroups, ether groups, or combinations thereof. More preferably, Zincludes urethane and/or urea groups, and most preferably, urethanegroups.

The precursors suitable for forming the B blocks of the A_(n)B blockcopolymers according to the present invention are preferablydiisocyanate terminated prepolymers. They are preferably, diisocyanatedterminated polyurethanes, polyureas, or poly(urethane-ureas), and morepreferably, diisocyanate terminated polyurethanes. These polymers canvary from hard and rigid to soft and flexible.

The preferred polymers used to form the B blocks of the A_(n)B blockcopolymers of the present invention can be homopolymers or copolymers,although preferably, they are random, block, or segmented copolymers(i.e., containing both hard and soft domains or segments).

Such polymers used to form the B blocks can be prepared using a varietyof techniques from polymerizable compounds (e.g., monomers, oligomers,or polymers). Such compounds include diols, diamines, or combinationsthereof, for example.

Although certain preferred polymers are described herein, the polymersused to form the B blocks of the A_(n)B block copolymers of thepreferred biomaterials in the medical devices of the present inventioncan be a wide variety of polymers that include urethane groups, ureagroups, or combinations thereof. Such polymers are prepared fromisocyanate-containing compounds, such as polyisocyanates (preferablydiisocyanates), and compounds having at least two hydrogen atomsreactive with the isocyanate groups, such as polyols and/or polyamines(preferably diols and/or diamines).

Typically, the preferred urethane- and/or urea-containing polymers usedto form the B block are made using polyisocyanates and polyols and/orpolyamides, including polyester, polyether, and polycarbonate polyols,for example, although such polyols are less preferred because theyproduce less biostable materials. The polyols and polyamines can bealiphatic, cycloaliphatic, aromatic, heterocyclic, or combinationsthereof.

Examples of suitable diols for preparing the B-block prepolymers includethose commercially available under the trade designation POLYMEG andother polyethers such as polyethylene glycol and polypropylene oxide,polybutadiene diol, dimer diol (e.g., that commercially available underthe trade designation DIMEROL (from Uniqema, New Castle, Del.)),polyester-based diols such as those commercially available under thetrade designations STEPANPOL (from Stepan Corp., Northfield, Ill.), CAPA(a polycaprolactone diol from Solvay, Warrington, Cheshire, UnitedKingdom), and TERATE (from Kosa, Houston, Tex.), poly(ethyleneadipate)diol, poly(ethylene succinate)diol, poly(1,4-butanedioladipate)diol, poly(caprolactone)diol, poly(hexamethylene phthalate)diol,and poly(1,6-hexamethylene adipate)diol, as well as polycarbonate-baseddiols such as poly(hexamethylene carbonate)diol.

Other polyols can be used as chain extenders to form the B blockprecursors, as is conventionally done in the preparation ofpolyurethanes, for example. Examples of suitable chain extenders include1,10-decanediol, 1,12-dodecanediol, 9-hydroxymethyl octadecanol,cyclohexane-1,4-diol, cyclohexane-1,4-bis(methanol),cyclohexane-1,2-bis(methanol), ethylene glycol, diethylene glycol,1,3-propylene glycol, dipropylene glycol, 1,2-propylene glycol,trimethylene glycol, 1,2-butylene glycol, 1,3-butanediol,2,3-butanediol, 1,4-butanediol, 1,5-pentanediol,1,6-hexanediol,1,2-hexylene glycol, 1,2-cyclohexanediol,2-butene-1,4-diol, 1,4-cyclohexanedimethanol,2,4-dimethyl-2,4-pentanediol, 2-methyl-2,4-pentanediol,1,2,4-butanetriol, 2-ethyl-2-(hydroxymethyl)-1,3-propanediol, glycerol,2-(hydroxymethyl)-1,3-propanediol, neopentyl glycol, pentaerythritol,and the like.

Examples of suitable polyamines (typically diamines) for making theB-block prepolymers include ethylenediamine, 1,4-diaminobutane,1,10-diaminodecane, 1,12-diaminododecane, 1,8-diaminooctane,1,2-diaminopropane, 1,3-diaminopropane, tris(2-aminoethyl)amine, lysineethyl ester, and the like.

Examples of suitable mixed alcohols/amines for making the B-blockprepolymers include 5-amino-1-pentanol, 6-amino-1-hexanol,4-amino-1-butanol, 4-aminophenethyl alcohol, ethanolamine, and the like.

Suitable isocyanate-containing compounds for preparation ofpolyurethanes, polyureas, or poly(urethanes-ureas), are typicallyaliphatic, cycloaliphatic, aromatic, and heterocyclic (or combinationsthereof) polyisocyanates. In addition to the isocyanate groups they caninclude other functional groups such as biuret, urea, allophanate,uretidine dione (i.e., isocyanate dimer), and isocyanurate, etc., thatare typically used in biomaterials. Suitable examples of polyisocyanatesinclude 4,4′-diisocyanatodiphenyl methane (MDI),4,4′-diisocyanatodicyclohexyl methane (HMDI),cyclohexane-1,4-diisocyanate, cyclohexane-1,2-diisocyanate, isophoronediisocyanate, tolylene diisocyanates, naphthylene diisocyanates,benzene-1,4-diisocyanate, xylene diisocyanates, trans-1,4-cyclohexylenediisocyanate, 1,4-diisocyanatobutane, 1,12-diisocyanatododecane,1,6-diisocyanatohexane, 1,5-diisocyanato-2-methylpentane,4,4′-methylenebis(cyclohexyl isocyanate), 4,4′-methylenebis(2,6-diethyphenyl isocyanate), 4,4′-methylenebis(phenylisocyanate), 1,3-phenylene diisocyanate, poly((phenylisocyanate)-co-formaldehyde), tolylene-2,4-diisocyanate,tolylene-2,6-diisocyanate, dimer diisocyanate, as well aspolyisocyanates available under the trade designations DESMODUR RC,DESMODUR RE, DESMODUR RFE, and DESMODUR RN from Bayer, and the like.

The relatively hard segments of the polymers of the present invention(typically present in the B blocks) are preferably fabricated from shortto medium chain diisocyanates and short to medium chain diols ordiamines, all of which preferably have molecular weights of less thanabout 1000. Appropriate short to medium chain diols, diamines, anddiisocyanates include straight chain, branched, and cyclic aliphatics,although aromatics can also be used. Examples of diols and diaminesuseful in these more rigid segments include both the short and mediumchain diols or diamines discussed above.

Methods of Preparing the Block Copolymers

The A_(n)B block copolymers of the present invention can be made by avariety of methods involving condensation polymerization such asmetathesis polymerization or reaction of complementary functionalgroups.

Preferably, the method includes reacting a substantially monofunctionalpoly(vinyl pyrrolidone) with a functionalized B-block precursorcomprising functional groups reactive with the functional groups of thepoly(vinyl pyrrolidone). Preferably, the substantially monofunctionalpoly(vinyl pyrrolidone) is hydroxyl terminated. Preferably, this isprepared by polymerizing N-vinyl pyrrolidone in the presence of ahydroxyl terminated chain transfer agent, such as isopropoxyethanol.Preferably, the functionalized B-block precursor is a diisocyanateterminated prepolymer that includes urethane groups, urea groups, amidegroups, imide groups, ether groups, or combinations thereof, and morepreferably urethane and/or urea groups.

The PVP (prepolymer) precursors, whether homopolymers or copolymers(which include two or more monomers), can be made using standardtechniques such as radical polymerication. They can be functionalizedusing radical polymerization in the presence of a functionalized chaintransfer agent. Examples of suitable functional groups includecarboxylic acid, amine, amide, and silane groups. Typical functionalizedchain transfer agents and reaction conditions are disclosed in theExamples Section below.

The B-block (prepolymer) precursor can be made using standardtechniques. For example, B-block prepolymers can be made usingcondensation polymerization, ring-opening metathesis polymerization, andradical polymerization. For example, B-block urethane-containingprepolymers can be made using standard polyurethane synthesistechniques. Typical conditions are disclosed in the Examples Sectionbelow.

Preferred conditions for forming the A_(n)B block copoloymers includethe use of an inert atmosphere (e.g., nitrogen or argon), temperaturesof about 20° C. to about 150° C. (more preferably, about 50° C. to about100° C.), reaction times of about 1 hour to about 3 days (morepreferably, about 1 hour to about 24 hours). The A- and B-block(prepolymer) precursors are typically combined under such conditions toform the A_(n)B block copolymers of the present invention.

Alternatively, the A_(n)B block copolymers of the present invention canbe made in one step. Typically, this involves combining the reactantsfor making the B-block precursor with the A-block precursor. This isexemplified in Example 14.

In addition to the A_(n)B block copolymers described herein,biomaterials of the invention can also include a variety of additives.These include antioxidants, colorants, processing lubricants,stabilizers, imaging enhancers, fillers, and the like.

Methods of Modifying a Surface

The block copolymers of the present invention are preferably used tomodify a surface of a medical device. This includes preparing an A_(n)Bblock copolymer and (subsequently or simultaneously) applying it to thesurface of the medical device in any of a wide variety of manners.

For example, the block copolymer can be applied to a surface out of asolution. This can be done, for example, by dip coating, roll coating,spraying, inkjet printing, or combinations thereof.

Suitable solvents for solution coating include, for example, dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, chloroform, water,isopropanol, ethanol, acetone, acetonitrile, dioxane, dimethylacetamide, N-methyl pyrrolidone, or combinations thereof. Preferredsolvents for solution coating include, for example, dimethyl formamide,dimethyl sulfoxide, tetrahydrofuran, dimethyl acetamide, N-methylpyrrolidone, water, or combinations thereof.

The polymer content of a coating solution depends in part on the desiredcoating weight. Typically, the polymer content of a coating solution isat least about 0.1 percent by weight (wt-%), and preferably at leastabout 1.0 wt-%, based on the total weight of the solution. Typically,the polymer content of a coating solution is no more than about 40 wt-%,and preferably no more than about 20 wt-%, based on the total weight ofthe solution.

The temperature for coating is preferably about 25° C., but can be aslow as about 0° C. and as high as the melting point of the polymer orthe boiling point of the solvent (whichever is lower). The time periodfor coating can be as short as 0.1 second (e.g., dipping), but not solong as would result in dissolution of the substrate polymer. Typically,no more than about 5 minutes is required.

The coated sample can be subjected to elevated temperatures. Typically,any temperature above room temperature but below the melting point ofeither the substrate polymer or the block copolymer of the presentinvention. A typical temperature is at least about 70° C. The exposuretime at this elevated temperature is sufficient to remove the solventand promote adhesion of the block copolymer of the present invention tothe substrate polymer. A typical time is at least about 18 hours.Simultaneously or subsequently, the coated sample could be subjected toreduced pressure (e.g., a vacuum) to enhance solvent removal.

In other embodiments, the block copolymer can be applied to a surface bycoextruding the block copolymer with a substrate polymer. In a typicalcoextrusion process, two or more polymers are simultaneously extruded bytwo or more extruders into a common die. These polymers are combined atthe extruder head to produce a multilayer structure. For example, if itis desired to make a catheter, a tube could be produced that has asandwich structure comprising the different polymers used in thecoextrusion.

Coextrusion permits the properties of the various polymers used in thecoextrusion process to be combined. For example, coextruding a polymerwith acceptable strength properties and a polymer with acceptableenvironmental resistance may create an article with both strength andenvironmental resistance. The multilayer structure created usingcoextrusion has the strong polymer sandwiched between layers of thepolymer with environmental resistance, thus permiting the creation ofthe article with the desired combination of properties. Coextrusion hascertain advantages over other methods of combining properties, includingcost effectiveness and the ability to alter the properties of thesurface of the inner lumen of small diameter tubing.

For successful co-extrusion, it is desirable for the polymers to havecompatible properties. This compatibility permits good adhesion betweenthe coextruded layers and ensures the integrity of the extruded article.One way of obtaining this compatibility is for the polymers to becoextruded to share at least one common block. For example, apolyurethane tube with different properties on the surface of the innerlumen may be created by coextruding the polyurethane with a copolymercomprising polyurethane blocks and blocks with the desired surfaceproperties.

Coextrusion conditions, e.g., temperature, pressure, flow rates, willvary depending on the polymers and can be determined by one of skill inthe art without undue experimentation. For guidance see the ExamplesSection below.

Coextrusion can also involve reactive coextrusion of one or more layers(e.g., substrate polymer layer lubricious coating layer). This typicallyinvolves combining prepolymers (e.g., A- and B-block prepolymers) in theextruder under conditions effective to cause reaction thereof.Alternatively, reactants for forming the prepolymers can be combined inthe extruder.

Reactive coextrusion can result in the in situ formation of block orgrafted copolymers or crosslinked copolymer structures at the interfacebetween the coextruded layers. This provides entanglement between thetwo layers and enhanced adhesion. As above, reactive coextrusionconditions will vary depending on the polymers and can be determined byone of skill in the art without undue experimentation. For guidance seethe Examples Section below.

Layers of A_(n)B copolymers of the present invention can be as thick asneeded for the intended purpose. Desirably, as thin a layer as possibleis used to provide the intended properties (e.g., lubricity). Forexample, coatings as thin as 1 micron and as thick as 0.4 mm have beenprepared with slippery properties.

The invention has been described with reference to various specific andpreferred embodiments and will be further described by reference to thefollowing detailed examples. It is understood, however, that there aremany extensions, variations, and modifications on the basic theme of thepresent invention beyond that shown in the examples and detaileddescription, which are within the spirit and scope of the presentinvention.

EXAMPLES Example 1 Synthesis of Hydroxyl-terminatedPoly(N-vinyl-pyrrolidone)

MATERIALS: The monomer N-vinyl-pyrrolidone was purchased from AldrichChemical Co., Milwaukee, Wis., and the NaOH inhibitor was removed byvacuum distillation. The monomer was stored in a freezer prior to use.All other reagents were used as received from Aldrich Chemical Co.,including: anhydrous diethyl ether, 2,2-azobisisobutyronitrile (AIBN),and the chain transfer agent 2-isopropoxyethanol.

SYNTHESIS: In an oven-dried, nitrogen-purged, 1000-mL, 3-neckround-bottomed flask equipped with a magnetic stir bar, thermocouple,oil bubbler, and heating mantle, 5.2 grams (g) N-vinyl-pyrrolidone and0.5 g AIBN were dissolved into 451.5 g (500 milliliters (mL))isopropoxyethanol chain transfer agent. Nitrogen gas was bubbled throughthe reaction solution for about 30 minutes with stirring, prior toactivating the AIBN with heat. The reaction mixture was slowly heated to80° C. Upon heating, the nitrogen sparge tube was pulled out of thesolution to purge the overhead space for the duration of the reaction.The reaction mixture was heated for 24 hours. The solution was thentransferred to a single-neck, 1000-mL, round-bottomed flask forroto-evaporation. Isopropoxyethanol (300 mL) was used to rinse thesolution out of the reaction vessel. The isopropoxyethanol wasevaporated at 50° C. and 18 mm Hg (2.4 kPa) until the total volumeremaining was approximately 25 mL. This concentrated solution was pouredinto a Waring blender containing cold ether. With fast stirring, a whiteprecipitate formed and was collected by filtration using a Buchnerfunnel. The product was a white powder and 1.62 g were obtained,corresponding to a 31% yield. The low yield was due to multipleprecipitation attempts before a successful procedure was established.The white powder was purified in a Soxhlet extraction set up containing500 mL ether. The extraction was run for 24 hours. The product was driedunder vacuum at 50° C. for three days to remove the ether.

The molecular weight data obtained by GPC was as follows: number averagemolecular weight (MN)=5570 g/mol, weight average molecular weight(MW)=9420 g/mol, polydispersity (PDI)=1.69. The hydroxyl functionalitywas confirmed by reacting the PVP-OH with an isocyanate-terminatedprepolymer, synthesized as in Example 2, made of diisocyanatodiphenylmethane (MDI) and poly(tetra-methylene oxide) (PTMO). The isocyanatepeak at 2270 cm⁻¹ that was present in the prepolymer IR spectrumdisappeared upon the addition of the PVP-OH. New peaks correspondingwith urethane linkages at 3266 cm⁻¹ and 1727 cm⁻¹ were present in the IRspectrum of the product. This data supports that the poly(vinylpyrrolidone) was hydroxyl-terminated.

Example 2 Synthesis of Isocyanate-teminated B-block Prepolymer

MATERIALS: QO POLYMEG 1000 (PTMO), which is a poly(tetra-methyleneoxide), was purchased from Penn Specialty Chemicals, Inc., Memphis,Tenn. The PTMO was dried under full vacuum at 100° C. Flaked MONDUR M(MDI) was purchased from Bayer Corporation, Rosemount, Ill. and storedin a freezer until use. Anhydrous dioxane was purchased from Aldrich andwas used as received.

SYNTHESIS: Inside a nitrogen-atmosphere glove box, 15.71 g (15.43 mmol)PTMO and 80 g anhydrous dioxane were added to a 3-neck 250-mLround-bottomed flask equipped with magnetic stir bar, thermocouple andair condenser for gas expansion. The solution was stirred and allowed toequilibrate at 73° C. before 4.32 g (17.21 mmol) MDI was added to thereaction vessel. The reaction mixture was heated up to 93° C. brieflyand the remainder of the reaction was run at 74° C. The reaction was runovernight and the viscosity was noticeably higher the next morning.

The reaction was monitored by IR spectroscopy. The NCO peak at 2270 cm⁻¹was initially very strong and there was a broad absorption around 3500cm⁻¹, corresponding to the PTMO hydroxyl groups. Eighteen hours later,the absorption around 3500 cm⁻¹ was gone and a new broad peak around3300 cm⁻¹ formed, indicating urethane bond formation. A small isocyanatepeak at 2270 cm⁻¹ remained, indicating the prepolymer wasisocyanate-terminated. The isocyanate groups of the prepolymer werequenched with ethanol prior to GPC analysis. The molecular weightresults by GPC were: MN=40,800 g/mol, MW=69,500 g/mol, PDI=1.71.

Example 3 Synthesis of a PVP-Polyurethane-PVP Block Copolymer

MATERIALS: Hydroxyl-terminated poly(N-vinyl pyrrolidone) (PVP-OH) wassynthesized as described in Example 1. Prior to this reaction the PVP-OHwas dried under full vacuum at 50° C. for two days. Theisocayanate-terminated B-block prepolymer was synthesized as describedin Example 2. Anhydrous dioxane and anhydrous dimethylacetamide (DMAC)were purchased and used as received.

SYNTHESIS: Inside a nitrogen atmosphere glove box, 0.4 g PVP-OH wasdissolved in 1.62 g anhydrous DMAC in a dry 20-mL screw-top reactiontube. Next, 2.16 g of a 20% solution of the isocyanate-terminatedB-block prepolymer in dioxane was added to the reaction vessel. Thereaction mixture was shaken and placed in a 60° C. oven inside thenitrogen glove box for eighteen hours. The reaction was monitored by IRspectroscopy. The isocyanate peak at 2270 cm⁻¹ that was present in theprepolymer spectrum disappeared upon the addition of the PVP-OH. Newpeaks corresponding with urethane linkages at 3266 cm⁻¹ and 1727 cm⁻¹were present in the spectrum of the product. The solvents were removedby roto-evaporation. The total yield of PVP-PU-PVP triblock copolymerwas 0.52 g, corresponding to a 65% yield.

The following summarizes the spectral properties observed by IR: 3266,2945, 2858, 1727, 1685, 1538, 1424, 1371, 1287, 1225, 1113 wavenumber(cm⁻¹). GPC data was reported as follows: MN=91,800 g/mol, MW=119,000g/mol, PDI=1.3. A second peak was observed that seems to correspond toexcess PVP-OH; MN=5570, MW=7860. The following spectral properties wereobserved by ¹³C NMR (CDCl₃): δ175, 78.5, 76.5, 75.8, 72.4, 70.6, 68.7,28.1, 26.4, 24.7, 18.3.

Example 4 Dip Coating of PVP-Polyurethane-PVP Block Copolymer in NMP

MATERIALS: The triblock copolymer synthesized as in Example 3 was usedalong with N-methyl-2-pyrrolidinone (NMP) received from Aldrich.PELLETHANE 75D polyurethane pellets, obtained from Dow Chemical,Midland, Mich., were dried under full vacuum at 80° C. for eighteenhours. The pellets were then pressed into 1.02 mm thick sheets at 230°C., using a Carver, Inc. Press, Model #2699. The PELLETHANE 75D sheetswere then cut into 2.5 cm by 10.2 cm strips for dip coating tests.

PROCEDURE: In a 50-mL round-bottomed flask, 0.06 g of the triblockcopolymer of Example 3 was dissolved into 3.88 g NMP solvent, making a1.5% polymer solution. A PELLETHANE sample was dipped in the polymer/NMPsolution for approximately 15 seconds. The sample was hung to dry in a70° C. oven for eighteen hours. The sample was then placed in a vial ofwater and placed on the shaker table for 20 minutes. The sample wasslippery to the touch, relative to the uncoated substrate. The coatingwas slightly opaque and pale yellow in color. The coating did not ruboff the substrate.

Example 5 Synthesis of Isocyanate-teminated B-Block Prepolymer

MATERIALS: QO POLYMEG 1000 (PTMO) was purchased from Penn SpecialtyChemicals, Inc., Memphis, Tenn. The PTMO was dried under full vacuum at100° C. Flaked MONDUR M (MDI) was purchased from Bayer Corporation andstored in a freezer until use. Anhydrous dioxane was purchased fromAldrich and was used as received.

SYNTHESIS: Inside a nitrogen atmosphere glove box, 15.7 g (15.43 mmol)PTMO and 80 g anhydrous dioxane were added to a 3-neck 250-mLround-bottomed flask equipped with magnetic stir bar, thermocouple, andair condenser for gas expansion. The solution was stirred and allowed toequilibrate at 70° C. before 4.33 g (17.21 mmol) MDI was added to thereaction vessel. A small drop, approximately 75 parts per million (ppm),of tin dilaurate catalyst was added. The reaction mixture was heated upto 93° C. briefly and the remainder of the reaction was run at 74° C.The reaction was run overnight and the viscosity was noticeably higherthe next morning.

The reaction was monitored by IR spectroscopy. The NCO peak at 2270 cm⁻¹was initially very strong and there was a broad absorption around 3500cm⁻¹, corresponding to the PTMO hydroxyl groups. Almost immediatelyafter adding the catalyst, the absorption around 3500 cm⁻¹ was gone anda new broad peak around 3300 cm⁻¹ formed, indicating urethane bondformation. A small isocyanate peak at 2270 cm⁻¹ remained, indicating theprepolymer was isocyanate-terminated. The isocyanate groups of theprepolymer were quenched with ethanol prior to GPC analysis. Themolecular weight results by GPC were: MN=47,200 g/mol, MW=73,500 g/mol,PDI=1.56. The following spectral properties were observed by ¹³C NMR(CDCl₃): δ153.9, 136.3, 136.1, 129.4, 118.8, 70.7, 70.6, 70.19, 40.58,26.5, 26.23, 25.9.

Example 6 Synthesis of Hydroxyl-Terminated Poly(N-vinylpyrrolidone)

MATERIALS: The monomer N-vinylpyrrolidone was purchased from Aldrich andthe NaOH inhibitor was removed by vacuum distillation. The monomer wasstored in a freezer prior to use. All other reagents were used asreceived from Aldrich, including: anhydrous diethyl ether,2,2-azobisisobutyronitrile (AIBN), and the chain transfer agent2-isopropoxyethanol.

SYNTHESIS: In an oven-dried, nitrogen purged 12-liter (L) 3-neckround-bottomed flask equipped with a magnetic stir bar, thermocouple,oil bubbler, heating mantle, and 500-mL addition flask, 800 gN-vinylpyrrolidone was mixed with 4558.25 g (5.04 L) isopropoxyethanolchain transfer agent. Nitrogen gas was bubbled through the reactionsolution for 24 hours with stirring. More isopropoxyethanol, 494.19 g(547 mL), was used to dissolve 2.902 g AIBN. The AIBN solution waspurged within the addition flask for one hour as the bulk reactionsolution was slowly heated to 80° C. The stop-cock of the addition flaskwas then opened, to add the purged AIBN solution to the 80° C. reactionsolution. The nitrogen sparge tube was pulled out of the reactionsolution to purge the overhead space for the duration of the reaction.The reaction mixture was heated for 24 hours. The roto-evaporator wasset up to directly add the reaction solution into the 3-L round-bottomedflask being rotated. The isopropoxyethanol was evaporated at 50° C. and18 mm Hg (2.4 kPa) until there was 1,505.4 g left in the round-bottomedflask. This concentrated solution was poured into a Waring blendercontaining cold ether. With fast stirring, a white precipitate formedand was collected by filtration on in a Buchner funnel. The product wasa white powder. The white powder was purified in a Soxhlet extractionset up containing 500 mL ether. The extractions were run for 72 hours.The product was dried under vacuum at 50° C. for three days to removethe ether.

The molecular weight data obtained by GPC was as follows: MN=19,200g/mol, MW=36,400 g/mol, PDI=1.90. The hydroxyl functionality wasconfirmed by reacting the PVP-OH with an isocyanate-terminatedprepolymer made of MDI and PTMO, as in example 2. The isocyanate peak at2270 cm⁻¹ that was present in the prepolymer IR spectrum disappearedupon the addition of the PVP-OH. New peaks corresponding with urethanelinkages at 3266 cm⁻¹ and 1727 cm⁻¹ were present in the IR spectrum ofthe product. This data supports that the poly(vinyl pyrrolidone) washydroxyl-terminated.

Example 7 Synthesis of PVP-Polyurethane-PVP Block Copolymer

MATERIALS: Hydroxyl-terminated poly(N-vinyl pyrrolidone) (PVP-OH) wassynthesized as described in Example 6. Prior to this reaction the PVP-OHwas dried under full vacuum at 50° C. for two days. Theisocyanate-terminated B-block prepolymer was synthesized as described inExample 5. Anhydrous Dioxane and anhydrous dimethylacetamide (DMAC) werepurchased and used as received.

SYNTHESIS: Inside a nitrogen atmosphere glove box, 5.08 g PVP-OH wasdissolved in 20.1 g anhydrous DMAC in a dry 30 milliliter (4-ounce)glass jar. Next, 25.44 g of 20% solution of the B-block prepolymer indioxane solution was added to the reaction vessel. The reaction mixturewas shaken and placed in a 60° C. oven inside the nitrogen glove box foreighteen hours. The reaction was monitored by IR spectroscopy. Theisocyanate peak at 2270 cm⁻¹ that was present in the prepolymer spectrumdisappeared upon the addition of the PVP-OH. New peaks correspondingwith urethane linkages at 3266 cm⁻¹ and 1727 cm⁻¹ were present in thespectrum of the product.

Example 8 Dip Coating of PVP-Polyurethane-PVP Block Copolymer in NMP

MATERIALS: The PVP-PU-PVP triblock copolymer synthesized as in Example 7was used along with N-methyl-2-pyrrolidinone (NMP) received fromAldrich. PELLETHANE 75D pellets were dried under full vacuum at 80° C.for eighteen hours. The pellets were then pressed into 1.02 mm thicksheets at 230° C., using a Carver, Inc. Press, Model #2699. ThePELLETHANE 75D sheets were then cut into 2.5 cm by 10.2 cm strips fordip coating tests.

PROCEDURE: In a 250-mL round-bottomed flask, 30.52 g of the PVP-PU-PVPtriblock copolymer was dissolved into approximately 100 mL NMP solvent,making a 30% polymer solution. A PELLETHANE sample was dipped in thepolymer/NMP solution for approximately 15 seconds. The sample was hungto dry in a 70° C. oven for eighteen hours and was then rinsed in water.The sample was slippery to the touch, relative to the uncoatedsubstrate. The coating was slightly opaque and pale yellow in color. Thecoating did not rub off the substrate.

Example 9 Dip Coating of PVP-Polyurethane-PVP Block Copolymer in NMP

MATERIALS: The PVP-PU-PVP triblock copolymer synthesized as in Example 7was used along with N-methyl-2-pyrrolidinone (NMP) received fromAldrich. GRILAMID (Nylon 11, sold by EMS-GRIVORY, Sumter, S.C.) pellets,were dried under full vacuum at 80° C. for eighteen hours. The pelletswere then pressed into 1.02 mm thick sheets at 230° C., using a CarverInc. Press, Model #2699. The PELLETHANE 75D sheets were then cut into2.5 cm by 10.2 cm strips for dip coating tests.

PROCEDURE: In a 250-mL round-bottomed flask, 30.52 g of the PVP-PU-PVPtriblock copolymer was dissolved into approximately 100 mL NMP solvent,making a 30% polymer solution. A GRILAMID sample was dipped in thepolymer/NMP solution for approximately 15 seconds. The sample was hungto dry in a 70° C. oven for eighteen hours and was then rinsed in water.The sample was slippery to the touch, relative to the uncoatedsubstrate. The coating was slightly opaque and pale yellow in color. Thecoating did not rub off the substrate.

Example 10 Synthesis of Isocyanate-terminated B-Block Prepolymer

MATERIALS: QO POLYMEG 1000 (PTMO) was purchased from Penn SpecialtyChemicals, Inc. The PTMO was dried under full vacuum at 100° C. FlakedMONDUR M (MDI) was purchased from Bayer Corp. and stored in a freezeruntil use. Anhydrous dioxane was purchased from Aldrich and was used asreceived.

SYNTHESIS: Inside a nitrogen-atmosphere glove box, 156.75 g (153.6 mmol)PTMO and 800.04 g anhydrous dioxane were added to a 3-neck 2-literround-bottomed flask equipped with magnetic stir bar, thermocouple andair condenser for gas expansion. The solution was stirred and allowed toequilibrate at 78° C. before 43.25 g (171.7 mmol) MDI was added to thereaction vessel. A small drop of tin dilaurate catalyst was added. Thereaction mixture was heated for eighteen hours at 82° C. The viscositywas noticeably higher the next day.

The reaction was monitored by IR spectroscopy. The NCO peak at 2270 cm⁻¹was initially very strong and there was a broad absorption around 3500cm⁻¹, corresponding to the PTMO hydroxyl groups. Upon completion of thereaction, the absorption around 3500 cm⁻¹ was gone and a new broad peakaround 3300 cm⁻¹ formed, indicating urethane bond formation. A smallisocyanate peak at 2270 cm⁻¹ remained, indicating the prepolymer wasisocyanate-terminated.

Example 11 Synthesis of PVP-Polyurethane-PVP Block Copolymer

MATERIALS: Hydroxyl-terminated poly(N-vinyl pyrrolidone) (PVP-OH) wassynthesized as described in Example 6. Prior to this reaction the PVP-OHwas dried under full vacuum at 50° C. for two days. Theisocyanate-terminated B-block prepolymer was synthesized as described inExample 10. Anhydrous dioxane and anhydrous dimethylacetamide (DMAC)were purchased and used as received.

SYNTHESIS: Inside a Nitrogen atmosphere glove box, 198.87 g PVP-OH wasdissolved in 794.79 g anhydrous DMAC in a dry 3-liter 3-neckround-bottomed flask. The flask was placed in a 60° C. oven inside thedry box until the PVP-OH dissolved. The entire prepolymer batchsynthesized in Example 10 was transferred to the 3-neck round-bottomedflask containing the PVP-OH in DMAC. The reaction mixture wasmagnetically stirred and heated with a heating mantle and temperaturecontroller set at 65° C. for eighteen hours. The reaction was monitoredby IR spectroscopy. The isocyanate peak at 2270 cm⁻¹ that was present inthe prepolymer spectrum disappeared upon the addition of the PVP-OH. Newpeaks corresponding with urethane linkages at 3266 cm⁻¹ and 1727 cm⁻¹were present in the spectrum of the product.

The block copolymer was precipitated using cold ether and a Waringblender. First, the polymer solution was poured into the blender. Next,cold ether was slowly added to the polymer solution with fast stirring.Once a cloudy suspension formed, more ether was quickly added toprecipitate the polymer. The final ratio by volume was 4:1 ether topolymer solution. The block copolymer formed very small particles thatwere small enough to go through filter paper. The suspension was allowedto settle out for 5 to 10 minutes, enabling the particles to coalesce.The polymer was then able to be filtered through a large mesh. Mesh wasused because regular filter paper immediately became clogged. Being bothhydrophilic and hydrophobic, the polymer still retained a lot of thesolvent. The polymer was scraped from the mesh into a pan lined withMYLAR film. The pan was placed into a vacuum oven equipped with a coldtrap to further remove the solvent. The temperature of the oven was setat 50° C. and a full vacuum was pulled. Once the full vacuum wasapplied, the nitrogen was turned on so the resulting pressure was 52 mmHg (1.0 pound per square inch (psi) above the full vacuum, 6.93 kPa) tocreate some flow within the chamber to aid in solvent removal. Aftereighteen hours, the polymer was a semi-hard sheet. The sheet of polymerwas placed in a mesh bag, submerged into liquid nitrogen, and brokenwith a mallet into pieces small enough to fit in the grinder. Thepolymer was ground into small pellets and placed back into a MYLAR-linedpan and into the vacuum oven to remove any remaining solvent. The oventemperature-was increased to 60° C. and the polymer dried under vacuumwith 52 mm (Hg (1 psi), 6.93 kPa) nitrogen purge for 72 hours. The yieldof the final block copolymer product was 230 g, corresponding to a 57.7%yield.

The following spectral properties were observed by ¹³C NMR (CDCl₃):δ175.3, 153.9, 136.1, 129.4, 118.9, 70.6, 70.19, 64.9, 44.9, 43.6, 42.0,40.5, 31.5, 26.5, 26.2, 25.8, 18.3. The following spectral propertieswere observed by proton NMR (CDCl₃): δ 7.0, 4.1, 3.3, 3.1, 2.6, 2.2,2.0, 1.64, 1.5, 1.3.

Example 12 Synthesis of a Citric Acid Triester

A 250-mL three-neck round-bottomed flask is outfitted with a magneticstirbar and thermocouple. A Dean-Stark trap is placed in the centralneck, and a condenser is connected to the trap. The assembled glasswareis placed in a heating mantle on a stirplate, and 192 milligrams (0.01mole) citric acid is added to the flask, followed by three equivalents(0.03 mole) of hydroxy-terminated PVP, 10 milligramspara-toluenesulfonic acid and 100 milliliters of toluene. The reactionmixture is stirred magnetically and heated to 50° C. Ten drops ofconcentrated sulfuric acid is added, and the reaction mixture is broughtto reflux. When no further water is collected in the trap, the flaskcontents are cooled to room temperature. The solid product is collectedby vacuum filtration.

Example 13 Synthesis of a Block Copolymer Based on the Citric AcidTriester

Ten grams of the triester synthesized in Example 12 are placed in a dry250-mL three-neck round-bottomed flask outfitted with a magnetic stirbarand a nitrogen inlet connected to a bubbler. The nitrogen flow isstarted, and 100 mL anhydrous tetrahydrofuran is added. Stirring isstarted and when the triester has dissolved, the tetrahydrofuransolution is transferred via cannula to a stirred flask containing astoichiometric amount of isocyanate-terminated prepolymer (made usingPOLYMEG and MDI, as in the previous examples). The mixture is heated to60° C. and stirring is continued until the reaction is complete asmeasured by disappearance of the isocyanate absorption peak at 2270reciprocal centimeters (cm⁻¹). The solvent is removed using a rotaryevaporator.

Example 14 One Step Synthesis of a PVP-PU-PVP Block Copolymer

MATERIALS: The hydroxyl-terminated poly (N-vinylpyrrolidone) synthesizedin Example 6 was used after drying under vacuum at 50° C. QO POLYMEG1000 (PTMO) was purchased from Penn Specialty Chemicals, Inc. The PTMOwas dried under full vacuum at 100° C. Flaked MONDUR M (MDI) waspurchased from Bayer Corporation and stored in a freezer until use.Anhydrous dioxane was purchased from Aldrich and was used as received.

SYNTHESIS: In a 250-mL dried round-bottomed flask, equipped with amagnetic stirbar and thermocouple, 5.03 g of hydroxyl terminatedpoly(vinyl pyrrolidone) and 3.96 g POLYMEG 1000 were mixed with 20.12 ganhydrous dioxane and 20.12 g anhydrous DMAC. A small drop of tindilaurate catalyst was added after an initial IR scan was taken. Afterthe solution was heated to 70° C., 1.29 g MDI was added. The solutionchanged from colorless to light yellow in color. After a few minutes,the solution turned darker yellow. The solution became noticeably moreviscous as the reaction progressed. The progress of the reaction wasmonitored by IR spectroscopy. After eighteen hours of reaction time, theNCO peak was no longer present in the IR spectrum, but the hydroxyl peakremained. An additional 0.23 g MDI was added to the solution and allowedto react for 24 hours. The IR spectrum showed the hydroxyl peak remainedunchanged, but the NCO peak disappeared. The solution was cooled to roomtemperature and precipitated into approximately 800 mL of cold ether.The polymer formed yellow-white granules, which were placed in a vacuumoven at 50° C. to remove residual solvent. A total of 8.58 g of polymerwas collected, corresponding to an 81.6% yield.

The GPC data was as follows: MN=24,800 g/mol, MW=64,700 g/mol, PDI=2.61.The molecular weight results correspond well with a block copolymer madewith the two-step method.

The following spectral properties were observed by ¹³C NMR (CDCl₃):δ175.3, 153.9, 136.1, 129.4, 118.9, 70.6, 70.19, 64.9, 44.9, 43.6, 42.0,40.5, 31.5, 26.5, 26.2, 25.8, 18.3. The following spectral propertieswere observed by proton NMR (CDCl₃): δ 7.0, 4.1, 3.3–3.8 (broad), 3.1(broad), 2.2, 2.0 (broad), 1.72, 1.64, 1.5, 1.3. The NMR spectracorrespond well with NMR spectra of block copolymers made with thetwo-step synthesis route.

Example 15 Dip Coating using the PVP-PU-PVP Block Copolymer Synthesizedby the One Step Method

MATERIALS: The PVP-PU-PVP triblock copolymer synthesized by the one stepmethod as in Example 14 was used along with N-methyl-2-pyrrolidinone(NMP) received from Aldrich. PELLETHANE 75D pellets were dried underfull vacuum at 80° C. for eighteen hours. The pellets were then pressedinto 0.1 cm (0.04 inch) thick sheets at 230° C., using a Carver Inc.Press, Model #2699. The PELLETHANE 75D sheets were then cut into 2.54 cm(one inch) by 10.2 cm (4 inch) strips for dip coating tests.

PROCEDURE: In a glass jar, a 20% solids solution was created bydissolving 1.31 g of the PVP-PU-PVP triblock copolymer in 5.2 g NMPsolvent. A PELLETHANE sample was dipped in the polymer/NMP solution forapproximately 15 seconds. The sample was hung to dry in a 70° C. ovenfor eighteen hours. The sample was rinsed with water and the coatingturned opaque white. The coated area was slippery to the touch, relativeto the uncoated substrate. The slip coating did not rub off thesubstrate.

Example 16 Synthesis of a Hydroxy-Terminated Copolymer of1-Vinyl-2-pyrrolidone and Methyl Acrylate

Five grams 1-vinyl-2-pyrrolidone (purified as noted previously inExample 1) and one gram methyl acrylate (vacuum distilled from calciumhydride) are placed in a three-neck one-liter flask outfitted with astirbar, sparge tube, thermocouple, and rubber septum. Then 500 mL2-isopropoxyethanol are added. The flask is placed in a heating mantleon a stirplate, and the contents are stirred magnetically. The reactionmixture is sparged with nitrogen for 60 minutes. The reaction mixture isheated to 80° C. during the sparging. Five hundred milligrams AIBN isdissolved in 10 mL 2-isopropoxyethanol in a septum-capped vial and thissolution is also sparged during this time (done by placing a hypodermicneedle attached to a nitrogen line through the septum into the solutionand an additional needle through the septum with its tip above thesolution). When sparging is complete and the large flask has reached theindicated temperature, the sparge tube is raised above the solutionmeniscus and the vial contents are transferred to the flask undernitrogen pressure using a double-ended needle. The contents are stirredat 80° C. for 24 hours. The 2-isopropoxyethanol is removed by rotaryevaporation, leaving a concentrated solution of approximately 25 mLvolume. The polymer is then isolated as described in Example 1.

Example 17 Synthesis of a Carboxylic Acid-Functionalized Chain TransferAgent

Five hundred grams of anhydrous 2-propanol (Aldrich) is added to a dry2-L three-neck round-bottomed flask outfitted with a magnetic stirbar,addition funnel, nitrogen inlet connected to a bubbler, andthermocouple. Five hundred milligrams of sodium are added and stirredfor one hour. Acrylonitrile (442 grams, one equivalent) is addeddropwise. The reaction mixture is stirred overnight. The product is thenadded to chloroform and washed sequentially with dilute aqueous HCl,saturated aqueous sodium bicarbonate, and deionized water. Thechloroform solution is then dried over anhydrous magnesium sulfate. Thechloroform is removed using a rotary evaporator, and the crude productdistilled. A portion of the resulting 2-cyanoethoxy-2-propane isdissolved in dry methanol acidified with HCl, and the solution isrefluxed for four hours. The excess methanol is removed under vacuumusing a rotary evaporator, and the crude ester then distilled undervacuum. This ester can be used as a chain transfer agent, or it may behydrolyzed to yield the desired 2-carboxyethoxy-2-propane.

Example 18 Synthesis of an Amine-Functionalized Chain Transfer Agent

A portion of the 2-cyanoethoxy-2-propane prepared above is reduced byheating at 70° C. with lithium aluminum hydride (0.5 M in diglyme,Aldrich) overnight. The resulting solution is cooled to room temperatureand poured on to ice. The mixture is extracted three times withchloroform. The chloroform solution is washed with distilled water andthen dried over anhydrous magnesium sulfate. The solvent is removed byrotary evaporation and the crude product distilled under vacuum.

Example 19 Synthesis of an Amide-Functionalized Chain Transfer Agent

A portion of the 2-cyanoethoxy-2-propane prepared above is converted tothe corresponding amide by heating at 50° C. in concentratedhydrochloric acid (HCl) for one hour. The mixture is then cautiouslypoured into a large volume of ice water, which is extracted withchloroform. The chloroform solution is washed twice with saturatedaqueous sodium bicarbonate, then with deionized water. The chloroform isremoved using a rotary evaporator.

Example 20 Synthesis of a Silane-Functionalized Chain Transfer Agent

Five hundred grams isopropyl vinyl ether (prepared by the method ofAdelman as reported in the Journal of the American Chemical Society,volume 75, pp. 2678–82 (1953)) is placed in a five-liter 3-neck flaskoutfitted with a magnetic stirbar, condenser, thermocouple, and additionfunnel. One milliliter platinum hydrosilylation catalyst solution(United Chemicals, Bristol, Pa., is added to the flask. Triethoxysilane(955 grams, 1 equivalent) is added to the addition funnel. The contentsof the flask are heated to 50° C. The heating mantle is turned off andthe triethoxysilane is added at a rate such that a gentle reflux ismaintained. After addition is complete, the reaction mixture is allowedto stir overnight. The platinum catalyst is removed using anamine-functionalized ion-exchange resin (AMBERLITE IRC-718), followed bypassing the product through a column containing neutral alumina. Thecrude 2-(triethoxysilyl)ethoxy-2-propane is then distilled under vacuum.

Example 21 Synthesis of PVP-PU-PVP with a Segmented Polyurethane Block

MATERIALS: QO POLYMEG 1000 (PTMO) was purchased from Penn SpecialtyChemicals, Inc. The PTMO was dried under full vacuum at 100° C. FlakedMONDUR M (MDI) was purchased from Bayer Corporation and stored in afreezer until use. Butane diol (BDO) was purchased from Aldrich and wasdried under full vacuum at 60° C. Anhydrous dioxane was purchased fromAldrich and was used as received.

SYNTHESIS: Inside a nitrogen-atmosphere glove box, 0.70 g BDO, 7.86 gPTMO and 51.50 g anhydrous dioxane were added to a 3-neck 500-mLround-bottomed flask equipped with magnetic stir bar, thermocouple, andair condenser for gas expansion. The solution was stirred and allowed.to equilibrate at 78° C. before 4.34 g MDI and one drop of tin dilauratecatalyst was added to the reaction vessel. The reaction mixture washeated for eighteen hours at 72° C.

The reaction was monitored by IR spectroscopy. The NCO peak at 2270 cm⁻¹was initially very strong and there was a broad absorption around 3500cm⁻¹, corresponding to the PTMO hydroxyl groups. Upon completion of thereaction, the absorption around 3500 cm⁻¹ was gone and a new broad peakaround 3300 cm⁻¹ formed, indicating urethane bond formation. A largeisocyanate peak at 2270 cm⁻¹ remained, indicating the prepolymer wasisocyanate-terminated. The molecular weight of this prepolymer wasdetermined by GPC relative to polystyrene standards. The MN=5900 g/mol,MW=11,100 g/mol, and the PDI was 1.88.

Hydroxyl-terminated poly(vinyl pyrrolidone) (PVP-OH), totaling 65.86 g,and 259.10 g anhydrous DMAC were mixed in a large glass vessel andplaced in a 60° C. oven to help the PVP-OH into solution. The PTMO/BDOprepolymer was transferred to a dry 1-liter 3-neck flask. ThePVP-OH/DMAC solution was added to the 1-liter round-bottomed flask andwas also used to rinse out the 500-mL round-bottomed flask. The reactionwas monitored by IR, and the isocyanate peak disappeared within twohours. The polymer was precipitated into a total of 2.5 liters of coldether. The yellow-white precipitate was filtered out in a Buchner funneland placed in a MYLAR-lined pan to dry under vacuum at 60° C. overnight.The yield was 48.79 g, corresponding to a 60.8% yield. The molecularweight of this block copolymer was determined by GPC relative topolystyrene standards. The MN=16,300 g/mol, MW=34,500 g/mol, and the PDIwas 2.12.

Example 22 Dip Coating using the PVP-PU-PVP Block Copolymer withSegmented Polyurethane Block

MATERIALS: The PVP-PU-PVP triblock copolymer with segmented polyurethaneblock, synthesized as in Example 21, was used along withN-methyl-2-pyrrolidinone (NMP) received from Aldrich. PELLETHANE 75D(segmented polyurethane sold by Dow Chemical, Midland, Mich.) pelletswere dried under full vacuum at 80° C. for eighteen hours. The pelletswere then pressed into 0.1 cm (0.04 inch) thick sheets at 230° C., usinga Carver Inc. Press, Model #2699. The PELLETHANE 75D sheets were thencut into 2.54 cm (one inch) by 10.2 cm (4 inch) strips for dip coatingtests.

PROCEDURE: In a glass jar, a 20% solids solution was created bydissolving 0.47 g segmented triblock copolymer in 1.8 g NMP solvent. APELLETHANE sample was dipped in the polymer/NMP solution forapproximately 15 seconds. The sample was hung to dry in a 70° C. ovenfor eighteen hours. The sample was rinsed with water and the coated areawas found to be slippery to the touch, relative to the uncoatedsubstrate. Although some of the coating rubbed off, the base layerremained and was slippery.

Example 23 Synthesis of an Isocyanatotelechelic Polyamide

A dry two-liter round-bottomed three-neck flask is outfitted with athermocouple, addition funnel, and condenser. A nitrogen inlet connectedto a bubbler is placed on top of the condensor and the flask is purgedwith nitrogen. One liter of anhydrous DMAC and fifty grams ofdiisocyanatohexane are added to the flask. Ten drops of dibutyltindilaurate is added to the flask. The contents of the flask are heated to70° C. with stirring. Sixty grams of 1,12-dodecanedioic acid aredissolved in a minimal amount of DMAC and the resulting solution istransferred to the addition funnel. The contents of the addition funnelare added dropwise, and the reaction stirred overnight. The product ofthe reaction is used without isolation, as described below.

Example 24 Synthesis of a PVP-Polyamide-PVP Block Copolymer

To the solution of isocyanatotelechelic polyamide synthesized in Example23 is added two equivalents of hydroxy-terminated PVP. Progress of thereaction is monitored by observing the disappearance of the isocyanateband in the IR at about 2270 cm⁻¹. The resulting polymer solution can beused as a polymer coating without isolation.

Example 25 Synthesis of an Isocyanatotelechelic Poly(amide-ether)

To the solution of the isocyanatotelechelic polyamide created in Example23 is added 18 grams POLYMEG (molecular weight 1000 g/mol). The reactionmixture is stirred an additional two hours at 70° C. and used directlyin the following example.

Example 26 Synthesis of a PVP-Poly(amide ether)-PVP Block Copolymer

To the solution of isocyanatotelechelic poly(amide-ether) synthesizedabove in Example 25 is added two equivalents of hydroxy-terminated PVP.Progress of the reaction is monitored by observing the disappearance ofthe isocyanate band in the IR at about 2270 cm⁻¹. The resulting polymersolution can be used as a polymer coating without isolation.

Example 27 Alternative Synthesis of a PVP-Poly(amide-ether)-PVP BlockCopolymer

A dry three-neck one-liter round-bottomed flask is outfitted with aheating mantle, stirbar, condenser, and thermocouple. A nitrogen inletconnected to a bubbler is placed on the condenser. Five hundredmilliliters anhydrous dioxane is added to the flask, followed by 60grams of bis(carboxymethoxy)polyethylene glycol (Aldrich) and one dropdibutyltin dilaurate. The contents of the flask are stirred magneticallyand heated to 50° C., then 27.53 grams of MDI are added to the flask.The mixture is brought to reflux and stirred eighteen hours, then 192grams hydroxy-terminated PVP is added. The mixture is then stirred 24hours. The polymer is precipitated into cold ether and dried in a vacuumoven at 50° C.

Example 28 Synthesis of an Isocyanatotelechelic Block Containing ImideGroups and Incorporation into an A-B-A Block Copolymer

A dry three-neck three-liter round-bottomed flask is outfitted with aheating mantle, stirbar, condenser with Dean-Stark trap, andthermocouple. A nitrogen inlet connected to a bubbler is placed on thecondenser. Two liters anhydrous m-cresol is added to the flask, followedby 218 grams 1,8-diaminooctane, 48 grams pyromellitic anhydride, and 500milligrams isoquinoline. The reaction is stirred and heated to refluxfor 8 hours. The product is precipitated by pouring into a large excessof cold, stirred methanol and vacuum filtered. It is washed withadditional cold methanol and then dried under vacuum. Ten grams of thisproduct is placed in a dry three-neck one-liter flask outfitted with aheating mantle, stirbar, condenser, and thermocouple. Five hundredmilliliters anhydrous N,N-dimethylacetamide is then placed in the flask,followed by one drop dibutyltin dilaurate and 19.2 grams ofhydroxy-terminated PVP of molecular weight 19,200 g/mol. The mixture isheated to 50° C. with stirring, then 17.8 grams MDI are added. Thereaction mixture is stirred overnight at 50° C. This solution can beused as a polymer coating with isolation. The polymer is isolated bypouring the solution into a large excess of cold, stirred methanol. Theproduct is filtered, washed with additional cold methanol, and driedunder vacuum.

Example 29 Synthesis of a PVP-Polyurea-PVP Block Copolymer

A dry three-neck one-liter round-bottomed flask is outfitted with aheating mantle, stirbar, condenser, and thermocouple. To the flask isadded 500 milliliters dioxane, one drop dibutyltin dilaurate, and 20 gbis(3-aminopropyl) terminated polytetrahydrofuran (Aldrich).

The contents of the flask are heated to 50° C. and 17.5 g MDI is added.After 4 hours, 19.2 g hydroxy-terminated PVP is added to the reactionmixture, and stirring is continued at 50° C. overnight. The resultingpolymer solution can be used as a polymer coating without isolation.

Example 30 Synthesis of a PVP-Polyester-PVP Block Copolymer

MATERIALS: Hydroxyl-terminated poly(vinyl pyrrolidone) (PVP-OH) was usedas synthesized in Example 6. DMAC (anhydrous) andtolylene-2,4-diisocyanate terminated poly(ethylene adipate) (MNapproximately 2700 g/mol) were purchased from Aldrich and used asreceived.

PROCEDURE: Into a dry 500-mL 3-neck round-bottomed flask, equipped withmagnetic stirbar, thermocouple and condenser, 108.05 g anhydrous DMACand 1.38 g tolylene-2,4-diisocyanate terminated poly(ethylene adipate)were mixed and heated to 70° C. PVP-OH was added in batches of about 5 guntil the NCO peak was no longer visible by IR. A total of 9.95 g PVP-OHwas added in total. The solution was heated for eighteen hours. Half ofthe reaction solution was then used to precipitate the polymer into 1.5liters (L) of cold ether. The other half was kept in the reactionsolution. The precipitate was a white powder that turned yellow andsticky within minutes. This was placed under vacuum to dry for 48 hours.The polymer was reprecipitated into 0.5 L cold ether, and placed backunder vacuum to dry. A total of 5.22 g of the PVP-Polyester-PVP blockcopolymer was isolated.

Example 31 Dip Coating using the PVP-Polyester-PVP Block Copolymer

MATERIALS: The PVP-Polyester-PVP Block Copolymer, synthesized as inExample 30, was used along with N-methyl-2-pyrrolidinone (NMP) receivedfrom Aldrich. PELLETHANE 75D (segmented polyurethane sold by DowChemical, Midland, Mich.) pellets were dried under full vacuum at 80° C.for eighteen hours. The pellets were then pressed into 0.1 cm (0.04inch) thick sheets at 230° C., using a Carver Inc. Press, Model #2699.The PELLETHANE 75D sheets were then cut into 2.54 cm (one inch) by 10.2cm (4 inch) strips for dip coating tests.

PROCEDURE: In a glass jar, a 20% solids solution was created bydissolving 0.389 g PVP-Polyester-PVP block copolymer in 1.54 g NMPsolvent. A PELLETHANE sample was dipped in the polymer/NMP solution forapproximately 15 seconds. The sample was hung to dry in a 70° C. ovenfor eighteen hours. The sample was rinsed with water and the coatingturned opaque white. The coated area was slippery to the touch, relativeto the uncoated substrate.

Example 32 Synthesis of a PVP-Polyester-PVP Block Copolymer containingBDO in the Polyester Segment

Materials: Hydroxyl-terminated poly(vinyl pyrrolidone) (PVP-OH) was usedas synthesized in Example 6. DMAC (anhydrous) andtolylene-2,4-diisocyanate terminated poly(ethylene adipate) (MNapproximately 2700 g/mol) were purchased from Aldrich and used asreceived. Butane diol(1,4) (BDO) was purchased from Aldrich and wasdried under full vacuum at 60° C.

Procedure: Into a dry 500-mL 3-neck round-bottomed flask, equipped withmagnetic stirbar, thermocouple, and condenser, 132.02 g anhydrous DMAC,0.35 g BDO, and 10.04 g tolylene-2,4-diisocyanate terminatedpoly(ethylene adipate) were mixed and heated to 70° C. An IR taken after20 minutes showed that all the hydroxyl groups had reacted, and an NCOpeak remained. A total of 6.03 g PVP-OH was then added and the solutionwas heated at 70° C. for eighteen hours. The IR showed no remaining NCOpeak and a small peak related to excess hydroxyl. The polymer was thenprecipitated into a blender containing cold ether. A total of 1.5 litersof ether was used in the precipitation. The polymer was stringy, unlikethe powder that formed in the PVP-polyester-PVP synthesis that did notcontain BDO. This could be an indication of higher molecular weight. Theproduct was placed under vacuum at 50° C. to dry for 48 hours. A totalof 12.46 g of the BDO-containing PVP-Polyester-PVP block copolymer wereisolated, corresponding to a 76% yield.

Example 33 Dip Coating using the PVP-Polyester-PVP Block CopolymerSynthesized with BDO

MATERIALS: The PVP-Polyester-PVP Block Copolymer containing BDO,synthesized as in Example 32, was used along withN-methyl-2-pyrrolidinone (NMP) received from Aldrich. PELLETHANE 75D(segmented polyurethane sold by Dow Chemical, Midland, Mich.) pelletswere dried under full vacuum at 80° C. for eighteen hours. The pelletswere then pressed into 0.1 cm (0.04 inch) thick sheets at 230° C., usinga Carver Inc. Press, Model #2699. The PELLETHANE 75D sheets were thencut into 2.54 cm (one inch) by 10.2 cm (4 inch) strips for dip coatingtests.

PROCEDURE: In a glass jar, a 20% solids solution was created bydissolving 0.459 g block copolymer in 1.84 g NMP solvent. A PELLETHANEsample was dipped in the polymer/NMP solution for approximately 15seconds. The sample was hung to dry in a 70° C. oven for eighteen hours.The sample was rinsed with water and the coating turned opaque white.The coated area was slippery to the touch, relative to the uncoatedsubstrate.

Example 34 Lubricity of a Polymer with a PVP-PU-PVP Block CopolymerCoating

An Imass Slip/Peel Tester Model SP-2000 was used to obtain quantitativedata regarding the lubricity of the block copolymer coating. Thecoefficient of friction (COF) was measured for uncoated GRILAMID (Nylon11) sheets and GRILAMID (Nylon 11) sheets coated with the blockcopolymer. The coating was applied to the GRILAMID (Nylon 11, sold byEMS-GRIVORY, Sumter, S.C.) sheets (after initial COF measurements) bydipping the sample into a solution of 20% block copolymer in NMP,followed by hanging the sample in a 70° C. oven for eighteen hours.

The ASTM method D-1894 was used as a guide for the determination of thecoefficient of friction. The coefficient of friction is the ratio of thenormal force (weight of the sled) over the tractive force, which is theforce required to initiate and maintain relative motion between thesurfaces. The GRILAMID surface was tested against PEBAX material(polyamide ether copolymer, sold by ATOFINA, Blooming Prairie, Minn.),which was attached to the 200 g sled. The GRILAMID surface was kept wetwith deionized water throughout the duration of t,he sled test. Theinstrument was set with the following parameters: 5 kg cell, 200 g sled(scaled to 208.6 g with the attached PEBAX), 2 second delay, 31 mm (1.22inch) distance, 10 seconds averaging, 152 mm/minute (6 inch/minute)speed. Five sled test runs were performed on the coated GRILAMID sheetand four runs were performed on the uncoated sheet. The results of theruns were averaged and are reported in the table below.

The static peak is defined as the maximum COF that occurs during thedelay time. The kinetic peak is the maximum COF that occurs during theaveraging time, while the valley reports the lowest COF measured duringthe averaging time. The reported average is an average of the COFmeasured during the ten second averaging time, and the root mean squared(RMS) shows the deviation from the average value.

GRILAMID Uncoated GRILAMID Coated Static Peak 0.249 0.064 Kinetic Peak0.206 0.024 Valley 0.147 0.002 *Average 0.175 0.006 RMS 0.011 0.003

The block copolymer coating decreased the average COF by more than 50%compared to the uncoated substrate.

Example 35 Preparation of Coextruded Tubing with a PVP-PU-PVP CopolymerCoating on the Surface of the Inner Lumen

A lubricious copolymer was coextruded with PELLETHANE 55D (PL55D)polyurethane pellets (obtained from Dow Chemical Co.) into tubing form.The PELLETHANE pellets were extruded with a single screw extruder(length to diameter (L/D) ratio of 24 and length (L) of 0.381 m (15inches)) with the temperature set at 249° C. (480° F), 257° C. (495°F.), and 254° C. (490° F.) in the feeding zone, melting zone, andpumping zone, respectively. The screw was operated at 42 revolutions perminute (rpm) with a pressure drop of 21 MPa to 26 MPa (3000 to 3700psi). The PVP-PU-PVP copolymer prepared as described in Example 11 wasextruded from an identical single screw extruder with the temperatureset at 204° C. (400° F.), 210° C. (410° F.), and 210° C. (410° F.) inthe feeding zone, melting zone, pumping zone, respectively. The feedrate of this extruder was adjusted to ensure the right coatingthickness. The extrudates from the two extruders met together in atubing co-extrusion die that was heated to 221–232° C. (430–450° F.) andconnected the two extruders. The die setup was such that the PVP-PU-PVPlayer created the inner layer of the lumen while the PELLETHANE polymercreated the outer layer of the lumen of the tubing. The two materialscontacted and welded for a time during running through the die on theorder of 10 seconds. The thickness of PVP-PU-PVP inner layer andPELLETHANE outer layer was controlled to be about 25.4 micrometers (μm)(0.001 inch) and 102 μm (0.004 inch), respectively, and the innerdiameter (ID) and outer diameter (OD) of the tubing were controlled tobe about 1.83 millimeters (mm) (0.072 inch) and 2.08 mm (0.082 inch),respectively, by adjusting the feeding rates (rpm) of the two extrudersand properly setting up the geometry of the die. As soon as theco-extruded tubing came out from the die, it was quench-cooled bypassing through a water tank. Thus, a tubing with the PELLETHANE layersleeving the PVP-PU-PVP layer was created.

Example 36 Preparation of Lubricious Coating by Reactive Lamination ofLubricious Poly(vinylpyrrolidone)-Poly(acrylic acid) Random Copolymer(VA) to PELLETHANE 75D (PL75D) Film

An alternative procedure to ensure the lubricious materials adherestrongly to the substrate involves reactive processing. To do this it ispreferred to select lubricious polymers that can chemically react withthe substrate. A copolymer composed of both the lubricious molecules andsubstrate molecules will form in situ during processing. This copolymerwill firmly stay at the interface between the lubricious coating and thesubstrate because it automatically entangles with the both sides. Inthis example, the reactive lubricious material was apoly(vinylpyrrolidone)-poly(acrylic acid) copolymer, 96 kg/mol, obtainedfrom Aldrich Chemical Co. In order to reduce the processing temperature,a low molecular weight (10 kg/mol) PVP, obtained from Aldrich ChemicalCo., was mixed with the copolymer in a weight ratio of 10:90 by blendingthe dry powders. The carboxylic acid group of the copolymer is thoughtto couple with the urethane or hydroxyl groups of PELLETHANE, resultingin the formation of a graft copolymer. Films of the mixture andPELLETHANE PL75D, obtained from Dow Chemical Co., were prepared at 230°C. (446° F.) for 5 to 10 minutes with a hot press. The two films werelaminated together at 230° C. (446° F.) for 5 to 10 minutes. Thepoly(vinylpyrrolidone)-poly(acrylic acid) side of the laminate waslubricious when it was wet, which lasted for two weeks.

Example 37 Preparation of Reactive-Coextruded Tubing with a Poly(vinylpyrrolidone)-Poly(acrylic acid) Random Copolymer Lubricious Coating onthe Surface of the Inner Lumen

The lubricious poly(vinylpyrrolidone)-poly(acrylic acid) copolymer(mixed with a low molecular weight (10 kg/mol) PVP in a weight ratio of10:90 as described in Example 36) was coextruded with PELLETHANE intotubing form. The PELLETHANE pellets were extruded with a single screwextruder as described in Example 35. The polymer mixture, prepared asdescribed in Example 36, was extruded from an identical single screwextruder with the temperature set at 204° C. (400° F.), 207° C. (405°F.) and 216° C. (420° F.) in the feeding zone, melting zone, pumpingzone, respectively. The feed rate of this extruder was adjusted toensure the right coating thickness. The extrudates from the twoextruders met together in a tubing co-extrusion die that was heated to221–232° C. (430–450° F.) and connected the two extruders. The die setupwas such that the poly(vinylpyrrolidone)-poly(acrylic acid) layercreated the inner layer of the lumen while the PELLETHANE polymercreated the outer layer of the lumen of the tubing. The two materialscontacted and welded for a time during running through the die on theorder of 10 seconds. The thickness of thepoly(vinylpyrrolidone)-poly(acrylic acid) inner layer and PELLETHANEouter layer was controlled to be about 25.4 μm and 102 μm, respectively,and the ID and OD of the tubing were controlled to be about 1.83 mm and2.08 mm, respectively, by adjusting the feeding rates (revolutions perminute, rpm) of the two extruders and properly setting up the geometryof the die. As soon as the co-extruded tubing came out from the die, itwas quench-cooled by passing through a water tank. Thus, a tubing withthe PELLETHANE layer sleeving the poly(vinylpyrrolidone)-poly(acrylicacid) layer was created.

Example 38 Lubricity Test of the Coextruded Tubing

An Imass Slip/Peel Tester Model SP-2000 was used to obtain quantitativedata regarding the lubricity of the inner lumen of PELLETHANE tubingcoextruded with the PVP-PU-PVP BLOCK copolymer of Example 11.

The ASTM method D-1894 was used as a guide for the determination of thecoefficient of friction. An experiment was set up to pull a smalldiameter PELLETHANE tube through the inner lumen of the coextrudedtubing of Example 35. A piece of tape was used to hold the coextrudedtubing stationary and to provide resistance by keeping the tubing flat.The smaller diameter PELLETHANE tube was connected to the slip tester,and was pulled 31 mm (1.22 inch) through the coextruded tubing for eachrun. The tubing was kept wet with deionized water throughout theduration of the sled test. The instrument was set with the followingparameters: 5 kg cell, 200 g sled, 2 second delay, 31 mm (1.22 inch)distance, 10 seconds averaging, 152 mm/minute (6 inch/minute) speed.Four sled test runs were performed on the coextruded tubing. The resultsof the runs were averaged and are reported in the table below. The sameexperiment was attempted on a sample of PELLETHANE tubing that wasextruded before the copolymer was added to the extruder. The uncoatedtubing did not allow the smaller diameter PELLETHANE tube to slide atall. Instead, the smaller PELLETHANE tube stretched as it was pulled,and COF measurements could not be made.

The static peak is defined as the maximum COF that occurs during thedelay time. The kinetic peak is the maximum COF that occurs during theaveraging time, while the valley reports the lowest COF measured duringthe averaging time. The reported average is an average of the COFmeasured during the ten second averaging time, and the root mean squared(RMS) shows the deviation from the average value.

Coextruded Tubing Static Peak 0.581 Kinetic Peak 0.750 Valley 0.533Average 0.671 RMS 0.050

This data indicates that the coextrusion of the PELLETHANE with thePVP-PU-PVP block copolymer substantially reduced the COF of the innerlumen, compared to regular PELLETHANE tubing.

The complete disclosure of all patents, patent documents, andpublications cited herein are incorporated by reference, as ifindividually incorporated. The foregoing detailed description andexamples have been given for clarity of understanding only. Nounnecessary limitations are to be understood therefrom. The invention isnot limited to the exact details shown and described, for variationsobvious to one skilled in the art will be included within the inventiondefined by the claims.

1. A medical device comprising a surface comprising a thermoplasticA_(n)B block copolymer, wherein the A block comprises poly(vinylpyrrolidone) units and the B block is a long-chain organic polymericconnecting unit comprising urethane groups, urea groups, imide groups,amide groups, ester groups, ether groups, or combinations thereof,wherein n is at least two, and further wherein the long-chain organicpolymeric connecting unit comprises 20 carbon atoms or more.
 2. Themedical device of claim 1 wherein the block copolymer is biocompatible.3. The medical device of claim 2 wherein the biocompatible block polymersubstantially maintains its physical properties and function during thetime it remains implanted or in contact with body fluids or tissues. 4.A medical device comprising a surface comprising a thermoplastic A_(n)Bblock copolymer, wherein the A block comprises poly(vinyl pyrrolidone)units and the B block is a long-chain organic polymeric connecting unitcomprising urethane groups, urea groups, imide groups, amide groups,ester groups, ether groups, or combinations thereof, wherein n is atleast two, and further wherein the long-chain organic polymericconnecting unit comprises 100 atoms or more.
 5. The medical device ofclaim 4 wherein the long-chain organic polymeric connecting unitcomprises 500 atoms or more.
 6. The medical device of claim 5 whereinthe long-chain organic polymeric connecting unit comprises 1000 atoms ormore.
 7. A method of modifying a surface of a medical device, the methodcomprising: preparing a thermoplastic A_(n)B block copolymer, whereinthe A block comprises poly(vinyl pyrrolidone) units and the B block is along-chain organic polymeric connecting unit comprising urethane groups,urea groups, imide groups, amide groups, ether groups, ester groups, orcombinations thereof, wherein n is at least two, and further wherein thelong-chain organic polymeric connecting unit comprises 20 carbon atomsor more; and applying the A_(n)B copolymer to the surface of the medicaldevice.
 8. The method of claim 7 wherein the block copolymer isbiocompatible.
 9. The method of claim 8 wherein the biocompatible blockcopolymer substantially maintains its physical properties and functionduring the time it remains implanted or in contact with body fluids ortissues.
 10. A method of modifying a surface of a medical device, themethod comprising: preparing a thermoplastic A_(n)B block copolymer,wherein the A block comprises poly(vinyl pyrrolidone) units and the Bblock is a long-chain organic polymeric connecting unit comprisingurethane groups, urea groups, imide groups, amide groups, ether groups,ester groups, or combinations thereof, wherein n is at least two, andfurther wherein the long-chain organic polymeric connecting unitcomprises 100 atoms or more; and applying the A_(n)B copolymer to thesurface of the medical device.
 11. The method of claim 10 wherein thelong-chain organic polymeric connecting unit comprises 500 atoms ormore.
 12. The method of claim 11 wherein the long-chain organicpolymeric connecting unit comprises 1000 atoms or more.
 13. Athermoplastic A_(n)B block copolymer, wherein the A blocks comprisepoly(vinyl pyrrolidone) units and the B block is a long-chain organicpolymeric connecting unit comprising urethane groups, urea groups, imidegroups, amide groups, ether groups, or combinations thereof, wherein nis at least two, and further wherein the long-chain organic polymericconnecting unit comprises 20 carbon atoms or more.
 14. The blockcopolymer of claim 13 wherein the block copolymer is biocompatible. 15.The block copolymer of claim 14 wherein the biocompatible blockcopolymer substantially maintains its physical properties and functionduring the time it remains implanted or in contact with body fluids ortissues.
 16. A thermoplastic A_(n)B block copolymer, wherein the Ablocks comprise poly(vinyl pyrrolidone) units and the B block is along-chain organic polymeric connecting unit comprising urethane groups,urea groups, imide groups, amide groups, ether groups, or combinationsthereof, wherein n is at least two, and further wherein the long-chainorganic polymeric connecting unit comprises 100 atoms or more.
 17. Theblock copolymer of claim 16 wherein the long-chain organic polymericconnecting unit comprises 500 atoms or more.
 18. The block copolymer ofclaim 17 wherein the long-chain organic polymeric connecting unitcomprises 1000 atoms or more.
 19. A method of preparing a thermoplasticA_(n)B block copolymer, the method comprising reacting a substantiallymonofunctional poly(vinyl pyrrolidone) with a functionalized B-blockprecursor comprising functional groups reactive with the functionalgroups of the poly(vinyl pyrrolidone) to form the thermoplastic A_(n)Bblock copolymer, wherein the A blocks comprise poly(vinyl pyrrolidone)units and the B block is a long-chain organic polymeric connecting unitcomprising urethane groups, urea groups, imide groups, amide groups,ether groups, or combinations thereof, wherein n is at least two, andfurther wherein the long-chain organic polymeric connecting unitcomprises 20 carbon atoms or more.
 20. A method of preparing athermoplastic A_(n)B block copolymer, the method comprising reacting asubstantially monofunctional poly(vinyl pyrrolidone) with afunctionalized B-block precursor comprising functional groups reactivewith the functional groups of the poly(vinyl pyrrolidone) to form thethermoplastic A_(n)B block copolymer, wherein the A blocks comprisepoly(vinyl pyrrolidone) units and the B block is a long-chain organicpolymeric connecting unit comprising urethane groups, urea groups, imidegroups, amide groups, ether groups, or combinations thereof, wherein nis at least two, and further wherein the long-chain organic polymericconnecting unit comprises 100 atoms or more.
 21. A method of preparing athermoplastic A_(n)B block copolymer, the method comprising reacting asubstantially monofunctional poly(vinyl pyrrolidone) with functionalizedB-block precursor reactants to form the thermoplastic A_(n)B blockcopolymer, wherein the A blocks comprise poly(vinyl pyrrolidone) unitsand the B block is a long-chain organic polymeric connecting unitcomprising urethane groups, urea groups, imide groups, amide groups,ether groups, or combinations thereof, wherein n is at least two, andfurther wherein the long-chain organic polymeric connecting unitcomprises 20 carbon atoms or more.
 22. A method of preparing athermoplastic A_(n)B block copolymer, the method comprising reacting asubstantially monofunctional poly(vinyl pyrrolidone) with functionalizedB-block precursor reactants to form the thermoplastic A_(n)B blockcopolymer, wherein the A blocks comprise poly(vinyl pyrrolidone) unitsand the B block is a long-chain organic polymeric connecting unitcomprising urethane groups, urea groups, imide groups, amide groups,ether groups, or combinations thereof, wherein n is at least two, andfurther wherein the long-chain organic polymeric connecting unitcomprises 100 atoms or more.